tbuckley/cabot-search huggingface dataset:
Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer
Authors: Fangyuan Zhao, Minoru Miyashita, Masaya Hattori, Toshio Yoshimatsu, Frederick Howard, Kristiyana Kaneva, Ryan Jones, Joshua S. K. Bell, Gini F. Fleming, Nora Jaskowiak, Rita Nanda, Yonglan Zheng, Dezheng Huo, Olufunmilayo I. Olopade
Journal: JAMA Network Open (2023)

Importance Among patients with breast cancer, inconsistent findings have been published on racial disparities in achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT). Objective To investigate whether racial disparities exist in achieving pCR and what factors contribute to them. Design, Setting, and Participants Within the ongoing Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), which consists of a prospectively ascertained cohort of patients with breast cancer, 690 patients with stage I to III breast cancer receiving NACT were identified for this single-institution study at the University of Chicago Medicine. Patients diagnosed between 2002 and 2020 (median follow-up: 5.4 years) were included; next-generation sequencing data on tumor-normal tissue pairs were available from 186 ChiMEC patients, including both primary and residual tumor samples. Statistical analysis was performed from September 2021 to September 2022. Exposures Demographic, biological, and treatment factors that could contribute to disparities in achieving pCR. Main Outcomes and Measures pCR was defined as the absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ. Results The study included 690 patients with breast cancer, with a mean (SD) age of 50.1 (12.8) years. Among the 355 White patients, 130 (36.6%) achieved pCR compared to 77 of the 269 Black patients (28.6%; P = .04). Not achieving pCR was associated with significantly worse overall survival (adjusted hazard ratio, 6.10; 95% CI, 2.80-13.32). Black patients had significantly lower odds of achieving pCR compared with White patients in the hormone receptor–negative/ ERBB2 + subtype (adjusted odds ratio, 0.30; 95% CI, 0.11-0.81). Compared with White patients with ERBB2 + disease, Black patients were more likely to have MAPK pathway alterations (30.0% [6 of 20] vs 4.6% [1 of 22]; P = .04), a potential mechanism of anti- ERBB2 therapy resistance. Tumor mutational burden and somatic alterations in several genes (eg, FGF4 , FGF3, CCND1, MCL1, FAT1, ERCC3, PTEN ) were significantly different between the primary and residual tumors. Conclusions and Relevance In this cohort study of patients with breast cancer, racial disparities in response to NACT were associated with disparities in survival and varied across different breast cancer subtypes. This study highlights the potential benefits of better understanding the biology of primary and residual tumors.
Comparison of Availability of Trial Results in ClinicalTrials.gov and PubMed by Data Source and Funder Type
Authors: Julianne T. Nelson, Tony Tse, Yvonne Puplampu-Dove, Elisa Golfinopoulos, Deborah A. Zarin
Journal: JAMA (2023)

This study examines the dissemination of trial results by data source (ie, ClinicalTrials.gov and PubMed) and funder type (ie, industry and nonindustry).
The Significance of a Pathologic Complete Response in Patients With Soft Tissue Sarcoma
Authors: Catherine S. Spina, Thomas F. DeLaney
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Continuous cuffless blood pressure monitoring with a wearable ring bioimpedance device
Authors: Kaan Sel, Deen Osman, Noah Huerta, Arabella Edgar, Roderic I. Pettigrew, Roozbeh Jafari
Journal: npj Digital Medicine (2023)

Smart rings provide unique opportunities for continuous physiological measurement. They are easy to wear, provide little burden in comparison to other smart wearables, are suitable for nocturnal settings, and can be sized to provide ideal contact between the sensors and the skin at all times. Continuous measuring of blood pressure (BP) provides essential diagnostic and prognostic value for cardiovascular health management. However, conventional ambulatory BP measurement devices operate using an inflating cuff that is bulky, intrusive, and impractical for frequent or continuous measurements. We introduce ring-shaped bioimpedance sensors leveraging the deep tissue sensing ability of bioimpedance while introducing no sensitivity to skin tones, unlike optical modalities. We integrate unique human finger finite element model with exhaustive experimental data from participants and derive optimum design parameters for electrode placement and sizes that yields highest sensitivity to arterial volumetric changes, with no discrimination against varying skin tones. BP is constructed using machine learning algorithms. The ring sensors are used to estimate arterial BP showing peak correlations of 0.81, and low error (systolic BP: 0.11 ± 5.27 mmHg, diastolic BP: 0.11 ± 3.87 mmHg) for >2000 data points and wide BP ranges (systolic: 89-213 mmHg and diastolic: 42-122 mmHg), highlighting the significant potential use of bioimpedance ring for accurate and continuous estimation of BP.
<i>Notes from the Field:</i> Cluster of Blastomycosis Among Neighborhood Residents — St. Croix County, Wisconsin, 2022
Authors: Hannah E. Segaloff, Karen Wu, Summer Shaw, Elizabeth M. Klasen, Lori Peterson, Sue Lindberg, Samantha L. Williams, Andrew Wiese, Yvonne M. Bellay, Meredith Smith, Kelli Engen, Mitsuru Toda, Suzanne Gibbons-Burgener
Journal: MMWR Morbidity and Mortality Weekly Report (2023)
Cardio‐hepatic syndrome in patients undergoing mitral valve transcatheter edge‐to‐edge repair
Authors: Lukas Stolz, Mathias Orban, Nicole Karam, Edith Lubos, Mirjam Wild, Ludwig Weckbach, Thomas J. Stocker, Fabien Praz, Daniel Braun, Kornelia Löw, Sebastian Hausleiter, Konstantin Stark, Philipp Doldi, Noemie Tence, Martin Orban, Satoshi Higuchi, Magda Haum, Stephan Windecker, Christian Hagl, Julia Mayerle, Michael Näbauer, Daniel Kalbacher, Steffen Massberg, Jörg Hausleiter
Journal: European Journal of Heart Failure (2023)

The impact of the cardio-hepatic syndrome (CHS) on outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) for relevant mitral regurgitation (MR) is unknown. The objectives of this study were three-fold: (i) to characterize the pattern of hepatic impairment, (ii) to investigate the prognostic value of CHS, and (iii) to evaluate the changes in hepatic function after M-TEER.Hepatic impairment was quantified by laboratory parameters of liver function. In accordance with existing literature, two types of CHS were distinguished: ischaemic type I CHS (elevation of both transaminases) and cholestatic type II CHS (elevation of two out of three parameters of hepatic cholestasis). The impact of CHS on 2-year mortality was evaluated using a Cox model. The change in hepatic function after M-TEER was assessed by laboratory testing at follow-up. We analysed 1083 patients who underwent M-TEER for relevant primary or secondary MR at four European centres between 2008 and 2019. Ischaemic type I and cholestatic type II CHS were observed in 11.1% and 23.0% of patients, respectively. Predictors for 2-year all-cause mortality differed by MR aetiology. While in primary MR cholestatic type II CHS was independently associated with 2-year mortality, ischaemic CHS type I was an independent mortality predictor in secondary MR patients. At follow-up, patients with MR reduction ≤2+ (obtained in 90.7% of patients) presented with improved parameters of hepatic function (median reduction of 0.2 mg/dl, 0.2 U/L and 21 U/L for bilirubin, alanine aminotransferase and gamma-glutamyl transferase, respectively, p < 0.01).The CHS is frequently observed in patients undergoing M-TEER and significantly impairs 2-year survival. Successful M-TEER may have beneficial effects on CHS.
Oncogenic long noncoding RNA LINC02283 enhances PDGF receptor A-mediated signaling and drives glioblastoma tumorigenesis
Authors: Anshika Goenka, Xiao Song, Deanna Tiek, Rebeca Piatniczka Iglesia, Minghui Lu, Chang Zeng, Craig Horbinski, Wei Zhang, Bo Hu, Shi-Yuan Cheng
Journal: Neuro-Oncology (2023)

Abstract Background Long noncoding RNAs (lncRNAs) regulate the etiology of complex diseases and cancers, including glioblastoma (GBM). However, lncRNA-based therapies are limited because the mechanisms of action of many lncRNAs with their binding partners are not completely understood. Methods We used transcriptomic and genomic data to analyze correlations between LINC02283 and PDGFRA (platelet-derived growth factor receptor A). The biological functions of the novel lncRNA were assessed in vivo using patient-derived glioma stem-like cells (GSCs), and orthotopic GBM xenografts. Immunoblotting, qRT-PCR, RNA pull down, crosslinked RNA immunoprecipitation, fluorescence in situ hybridization, and antisense oligo-mediated knockdown were performed to explore the regulation of LINC02283 on PDGFRA signaling. Expression of LINC02283 in clinical samples was assessed using pathologically diagnosed GBM patient samples. Results We identified a novel oncogenic lncRNA, LINC02283, that is highly expressed in the PDGFRA mutation-driven cohort of glioma patients and associated with worse prognosis. LINC02283 gene co-amplifies with the PDGFRA locus and shows high correlation with PDGFRA expression. Deprivation of LINC02283 in GSCs with PDGFRA amplification mutation, attenuated tumorigenicity and enhanced survival in orthotopic GBM xenograft models, while overexpression of LINC02283 in GSCs with wild-type PDGFRA, enhances PDGFRA signaling, and decreases survival. Further, LINC02283 interacts with PDGFRA to enhance its signaling and that of its downstream targets AKT and ERK, thus promoting oncogenesis in GBM. Conclusions Our results provide strong evidence of LINC02283 as a regulator of PDGFRA oncogenic activity and GBM malignancy and support the potential of lncRNAs as possible therapeutic targets.
Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study
Authors: Jenny Lee, Max Westphal, Yasaman Vali, Jerome Boursier, Salvatorre Petta, Rachel Ostroff, Leigh Alexander, Yu Chen, Celine Fournier, Andreas Geier, Sven Francque, Kristy Wonders, Dina Tiniakos, Pierre Bedossa, Mike Allison, Georgios Papatheodoridis, Helena Cortez-Pinto, Raluca Pais, Jean-Francois Dufour, Diana Julie Leeming, Stephen Harrison, Jeremy Cobbold, Adriaan G. Holleboom, Hannele Yki-Järvinen, Javier Crespo, Mattias Ekstedt, Guruprasad P. Aithal, Elisabetta Bugianesi, Manuel Romero-Gomez, Richard Torstenson, Morten Karsdal, Carla Yunis, Jörn M. Schattenberg, Detlef Schuppan, Vlad Ratziu, Clifford Brass, Kevin Duffin, Koos Zwinderman, Michael Pavlides, Quentin M. Anstee, Patrick M. Bossuyt
Journal: Hepatology (2023)

Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD.Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS ≥ 4;53%), at-risk NASH (NASH with F ≥ 2;35%), significant (F ≥ 2;47%), and advanced fibrosis (F ≥ 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82).Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.
Deep phenotype characterization of hypertensive response to exercise: implications on functional capacity and prognosis across the heart failure spectrum
Authors: Nicola Riccardo Pugliese, Nicolò De Biase, Lavinia Del Punta, Alessio Balletti, Silvia Armenia, Simona Buralli, Alessandro Mengozzi, Stefano Taddei, Marco Metra, Matteo Pagnesi, Barry A. Borlaug, Bryan Williams, Stefano Masi
Journal: European Journal of Heart Failure (2023)
Oral Delivery of Protein Drugs via Lysine Polymer‐Based Nanoparticle Platforms
Authors: Shuyan Han, Peikun Xin, Qilun Guo, Zhong Cao, Hai Huang, Jun Wu
Journal: Advanced Healthcare Materials (2023)

Oral delivery of proteins has opened a new perspective for the treatment of different diseases. However, advances of oral protein formulation are usually hindered by protein susceptibility and suboptimal absorption in the gastrointestinal tract (GIT). Polymeric nano drug delivery systems are considered revolutionary candidates to solve these issues, which can be preferably tunable against specific delivery challenges. Herein, a tailored family of lysine-based poly(ester amide)s (Lys-aaPEAs) is designed as a general oral protein delivery platform for efficient protein loading and protection from degradation. Insulin, as a model protein, can achieve effective internalization by epithelial cells and efficient transport across the intestinal epithelium layer into the systemic circulation, followed by controlled release in physiological environments. After the oral administration of insulin carried by Lys-aaPEAs with ornamental hyaluronic acid (HA), mice with type 1 diabetes mellitus showed an acceptable hypoglycemic effect with alleviated complications. A successful oral insulin delivery is associated with patient comfort and convenience and simultaneously avoids the risk of hypoglycemia compared with injections, which is of great feasibility for daily diabetes therapy. More importantly, this versatile Lys-aaPEAs polymeric library can be recognized as a universal vehicle for oral biomacromolecule delivery, providing more possibilities for treating various diseases.
Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles
Authors: Mei Lu, Haonan Xing, Wanxuan Shao, Pengfei Wu, Yuchuan Fan, Huining He, Stefan Barth, Aiping Zheng, Xing-Jie Liang, Yuanyu Huang
Journal: Acta Pharmaceutica Sinica B (2023)

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.
How I Treat Refractory CRS and ICANS Following CAR T-cell Therapy
Authors: Michael D. Jain, Melody Smith, Nirali N Shah
Journal: Blood (2023)

The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly due to expanding indications for standard of care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential to facilitating the widespread use. Pre-emptive interventions to prevent more severe toxicities has improved safety, facilitating CAR T-cell therapy in medically frail populations and those at high-risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic, as it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk-factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities.
ROS‐Scavenging Hydrogels Synergize with Neural Stem Cells to Enhance Spinal Cord Injury Repair via Regulating Microenvironment and Facilitating Nerve Regeneration
Authors: Dun Liu, Geng Lu, Bo Shi, Huanyu Ni, Jun Wang, Yong Qiu, Lin Yang, Zezhang Zhu, Xuan Yi, Xiao Du, Benlong Shi
Journal: Advanced Healthcare Materials (2023)

Abstract Although stem cell‐based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)‐abundant and hyper‐inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO 2 @BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS‐scavenging hydrogel (CeNP‐Gel). CeNP‐Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments and improving the viability of encapsulated NSCs. More interestingly, in the presence of CeNP‐Gel, microglial polarization to anti‐inflammatory M2 subtype are obviously facilitated, which is further verified to be associated with phosphoinositide 3‐kinase/protein kinase B pathway activation. Additionally, the injectable ROS‐scavenging hydrogel is confirmed to induce the integration and neural differentiation of transplanted NSCs. Compared with the blank‐gel group, the survival rate of NSCs in CeNP‐Gel group is about 3.5 times higher, and the neural differentiation efficiency is about 2.1 times higher. Therefore, the NSCs‐laden ROS‐scavenging hydrogel represents a comprehensive strategy with great application prospect for the treatment of SCI through comprehensively modulating the adverse microenvironment.
STAT5 activation promotes progression and chemotherapy-resistance in early T-cell precursor acute lymphoblastic leukemia
Authors: Cedric S. Tremblay, Jesslyn Saw, Jacqueline A Boyle, Katharina Haigh, Veronique Litalien, Hannah Ruth McCalmont, Kathryn Evans, Richard B Lock, Stephen M Jane, Jody J Haigh, David J Curtis
Journal: Blood (2023)
CHROMATIN ACTIVATION PROFILING OF STEREOTYPED CHRONIC LYMPHOCYTIC LEUKEMIAS REVEALS A SUBSET #8 SPECIFIC SIGNATURE
Authors: Maria Tsagiopoulou, Vicente Chapaprieta, Nuria Russiñol, Beatriz García-Torre, Nikolaos Pechlivanis, Ferran Nadeu, Nikos Papakonstantinou, Niki Stavroyianni, Anastasia Chatzidimitriou, Fotis Psomopoulos, Elías Campo, Kostas Stamatopoulos, Jose I. Martin-Subero
Journal: Blood (2023)
Smoking Cessation After Diagnosis of Kidney Cancer Is Associated With Reduced Risk of Mortality and Cancer Progression: A Prospective Cohort Study
Authors: Mahdi Sheikh, Anush Mukeriya, Hana Zahed, Xiaoshuang Feng, Hilary A. Robbins, Oxana Shangina, Vsevolod Matveev, Paul Brennan, David Zaridze
Journal: Journal of Clinical Oncology (2023)

PURPOSE To investigate whether postdiagnosis smoking cessation may affect the risk of death and disease progression in patients with renal cell carcinoma (RCC) who smoked at the time of diagnosis. METHODS Two hundred twelve patients with primary RCC were recruited between 2007 and 2016 from the Urological Department in N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia. Upon enrollment, a structured questionnaire was completed, and the patients were followed annually through 2020 to repeatedly assess their smoking status and disease progression. Survival probabilities and hazards for all-cause and cancer-specific mortality and disease progression were investigated using extended the Kaplan-Meier method, time-dependent Cox proportional hazards regression, and Fine-Gray competing-risk models. RESULTS Patients were followed for a median of 8.2 years. During this time, 110 cases of disease progression, 100 total deaths, and 77 cancer-specific deaths were recorded. Eighty-four patients (40%) quit smoking after diagnosis. The total person-years at risk for this analysis were 748.2 for continuing smoking and 611.2 for quitting smoking periods. At 5 years of follow-up, both overall survival (85% v 61%) and progression-free survival (80% v 57%) rates were higher during the quitting than continuing smoking periods (both P &lt; .001). In the multivariable time-dependent models, quitting smoking was associated with lower risk of all-cause mortality (hazard ratio [HR], 0.51; 95% CI, 0.31 to 0.85), disease progression (HR, 0.45; 95% CI, 0.29 to 0.71), and cancer-specific mortality (HR, 0.54; 95% CI, 0.31 to 0.93). The beneficial effect of quitting smoking was evident across all subgroups, including light smokers versus moderate-heavy smokers and those with early-stage versus late-stage tumors. CONCLUSION Quitting smoking after RCC diagnosis may significantly improve survival and reduce the risk of disease progression and cancer mortality among patients who smoke.